1-241683520-T-G

Position:

• chr1-241683520-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001367482.1(WDR64):​c.658T>G​(p.Cys220Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,399,502 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: WDR64 NM_001367482.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.34

Genes affected

WDR64 (HGNC:26570): (WD repeat domain 64)

LOC124904603 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR64	NM_001367482.1	c.658T>G	p.Cys220Gly	missense_variant	7/28	ENST00000437684.7
LOC124904603	XR_007067055.1	n.190-6020A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR64	ENST00000437684.7	c.658T>G	p.Cys220Gly	missense_variant	7/28	1	NM_001367482.1	P1
WDR64	ENST00000366552.6	c.628T>G	p.Cys210Gly	missense_variant	6/27	5
WDR64	ENST00000461971.5	n.519T>G		non_coding_transcript_exon_variant	6/6	5
WDR64	ENST00000425826.3	c.658T>G	p.Cys220Gly	missense_variant, NMD_transcript_variant	7/29	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000127 AC: 2 AN: 157344 Hom.: 0 AF XY: 0.0000120 AC XY: 1 AN XY: 83160

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000183

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1399502 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 690242

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000280

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000172

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 27, 2022

The c.628T>G (p.C210G) alteration is located in exon 6 (coding exon 6) of the WDR64 gene. This alteration results from a T to G substitution at nucleotide position 628, causing the cysteine (C) at amino acid position 210 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	18
DANN	Benign	0.90
DEOGEN2	Benign	0.069	T
Eigen	Benign	-0.020
Eigen_PC	Benign	-0.014
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.4	M
MutationTaster	Benign	0.80	D;D
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.21
Sift	Benign	0.24	T
Sift4G	Benign	0.12	T
Vest4		0.71
MutPred		0.46		Loss of stability (P = 0.0516);
MVP		0.23
MPC		0.41
ClinPred		0.46	T
GERP RS		4.1
Varity_R		0.29
gMVP		0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1490250215; hg19: chr1-241846822;